N Kozma | PubMed Health

PubMed2005

Progesterone-dependent immunomodulation.

The biological effects of progesterone are mediated by a 34-kDa protein named the progesterone-induced blocking factor (PIBF). PIBF, synthesized by lymphocytes of healthy pregnant women in the presence of progesterone, inhibits arachidonic acid release as well as NK activity, and modifies the cytokine balance. Within the cell the full-length PIBF is associated with the centrosome, while secretion of shorter forms is induced by activation of the cell. PIBF induces nuclear translocation of STAT6 as well as PKC phosphorylation and exerts a negative effect on STAT4 phosphorylation. The concentration of PIBF in pregnancy urine is related to the positive or negative outcome of pregnancy; furthermore, premature pregnancy termination is predictable by lower than normal pregnancy PIBF values. In vivo data suggest the biological importance of the above findings. Treatment of pregnant Balb/c mice with the antiprogesterone RU 486 results in an increased resorption rate, which is associated with the inability of spleen cells to produce PIBF. High resorption rates induced by progesterone receptor block as well as those due to high NK activity are corrected by simultaneous PIBF treatment.

Abortifacient Agents, Steroidal↗

PubMed2003

Progesterone regulates IL12 expression in pregnancy lymphocytes by inhibiting phospholipase A2.

PROBLEM: Progesterone-induced blocking factor (PIBF) is one of the pathways that mediate the immunological effects of progesterone. PIBF inhibits natural killer (NK) cytotoxic activity. Recently we showed that neutralization of PIBF results in an increased interleukin (IL)-12 expression, which is corrected by cyclooxygenase inhibitors. As exogenous arachidonic acid (AA) voids the NK blocking effect of PIBF, it is likely that PIBF acts before the level of the cyclooxygenase enzyme. Therefore in this study we investigated the effect of PIBF neutralizing antibody and simultaneous phospholipase A2 inhibitor quinacrine (Q) treatment on IL-12 production. METHODS: Pregnancy lymphocytes were treated with anti-PIBF antibody or lipopolysaccharide (LPS) as a positive control, in the presence or absence of Q. IL-12 expression by PBMC was detected by immunocytochemistry. RESULTS: Neutralization of PIBF as well as LPS treatment resulted in an increased IL-12 expression, which was corrected by simultaneous Q treatment. Pre-treatment of lymphocytes with progesterone prevented the stimulating effect of LPS on IL-12 production. CONCLUSION: Progesterone binding of the lymphocytes is followed by the release of PIBF that inhibits AA release. The subsequent block of prostaglandin synthesis reduces IL-12 production and results in a lowered cytotoxic NK activity, which may contribute to a normal pregnancy outcome.

Antibodies↗